1. Field of the Invention
This invention relates to derivatives of .alpha.,D-glucofuranose and .alpha., D-allofuranose compounds and intermediates for preparing these derivatives. More particularly, this invention relates to 1,2 and 1,2:3,5-O-isopropylidene-.alpha.,D-glucofuranose derivatives or .alpha.,D-allofuranose. The derivatives of this invention are useful for treating animals and mammals with inflammatory and/or autoimmune disorders such as psoriasis, atopic dermatitis, rheumatoid arthritis, osteoarthritis, scleroderma and systemic lupus erythematosus.
2. Description of the Related Art
Blocked acetals of hexoses exist as solids or liquids at room temperature. Various blocking methods are described in U.S. Pat. Nos. 2,715,121 and 4,056,322, the disclosures of which are incorporated by reference herein in their entireties. For example, in instances where an aldehyde or ketone is reacted with the hydroxyl groups on adjacent or neighboring sugar carbon atoms, the hexose may be blocked in a plurality of positions, such as, e.g., the 1,2- and/or 5,6- positions. In the 1,2:5,6-blocked hexoses the ring forms between carbons 1 and 4, leaving carbon 3 free to etherize; in the 1,2:3,5-blocked hexoses, the ring forms between carbons 1 and 4, leaving carbon 6 free to etherize; and in 1,2:4,6-blocked hexoses, the ring forms between carbons 1 and 2, again leaving carbon 3 free to etherize. Thus, 1,2:5,6-blocked hexoses may form 3-0 ethers, 1,2:3,5-blocked hexoses may form 6-O ethers, and 1,2:4,6-blocked hexoses may also form 3-0 ethers
After the desired blocking of the monosaccharide is obtained, the unblocked position of the monosaccharide can be etherized. Ethereal substituted hexose monosaccharides, such as 1,2:5,6-Di-O-isopropylidene 3-0-3('N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose (i.e. THERAFECTIN.RTM.), amiprilose hydrochloride are known and have demonstrated utility in managing the signs and symptoms of rheumatoid arthritis. These compounds have activity more generally as immuno-modulators, and therefore have a therapeutic effect on other autoimmune disorders such as psoriasis, eczema or lupus.
For certain indications, high doses of these monosaccharides, such as THERAFECTIN.RTM., are needed to produce effective results. These compound, however, can be topically applied. It is therefore an object of the present invention to provide an .alpha.,D-glucofuranose or .alpha.,D-allofuranose compound that exhibits greater potency than THERAFECTIN.RTM. when orally administered.
With respect to 1,2:3,5-Di-O-isopropylidene,-.alpha.,D-glucofuranose, the literature discloses its formation in trace to small quantities as a by-product of chemistries using glucose, acetone or other carbohydrates, (D. C. C. Smith, Journal of Chemical Society, 1956, 1244-1247). This compound is, however, prepared in poor yield and with a difficult work up from classical organic chemical reactions as described elsewhere in the literature.
It is therefore also an object of the present invention to provide a simple and efficient process for preparing 1,2:3,5-Di-O-isopropylidene-.alpha.,D-glucofuranose.
Additional objects and advantages of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and obtained by means of the mechanisms and combinations pointed out in the appended claims.